Embryo Project Encyclopedia Articles

Isotretinoin is a molecule and a byproduct (metabolite) of vitamin A, and in greater than normal amounts in pregnant women, it can cause fetal abnormalities including cleft lips, ear and eye defects, and mental retardation. Isotretinoin is commonly called by its trade name Accutane, and it's a chemical compound derived from vitamin A, or retinoic acid. Doctors prescribe isotretinoin to treat severe acne. For pregnant women, too much vitamin A or isotretinoin can also cause greater than normal rates of stillbirths and fetal disintegrations after the ninth week of gestation. Women who use isotretinoin during the first trimester of their pregnancies, even in small amounts, risk defects to their fetuses such as external ear malformations, cleft palates, undersized jaws (micrognathia), a variety of heart defects, buildups of fluids inside the skulls that leads to brain swelling (hydrocephalus), small heads and brains (microcephaly), and mental retardation.

Orchiopexy, also known as orchidopexy, is a surgical technique that can correct cryptorchidism and was successfully performed for one of the first times in 1877 in Scotland. Cryptorchidism, a condition where one or both of the testicles fail to descend before birth, is one of the most common male genital birth defects, affecting approximately 2 to 8 percent of full-term male infants, and around 33 percent of premature infants. Typically in the womb, male testes form within the abdomen, then descend into the scrotal area between twenty-five to thirty-five weeks’ gestation. If one or both testicles fail to descend before birth, physicians use orchiopexy to surgically relocate the undescended testes to their normal position in the scrotum. According to many researchers, most cases of cryptorchidism do not resolve on their own, and therefore, orchiopexy surgery is often necessary. Orchiopexy, when performed before puberty, can decrease the risk of testicular cancer and infertility associated with cryptorchidism.

First manufactured in 1988 by Serono laboratories, recombinant gonadotropins are synthetic hormones that can stimulate egg production in women for use in fertility treatments. Recombinant gonadotropins are artificially created using recombinant DNA technology, a technology that joins together DNA from different organisms. In vertebrates, naturally-occurring gonadotropins regulate the growth and function of the gonads, known as testes in males and ovaries in females. Medical professionals can derive female gonadotropins from the urine of pregnant and post-menopausal women, often using it to facilitate in vitro fertilization, or IVF. With the rapid development of assisted reproductive technologies like IVF, demand for human-derived gonadotropins rose to a global yearly demand of 120 million liters of urine by the beginning of the twenty-first century, which resulted in a demand that could not be met by traditional technologies at that time. Therefore, researchers created recombinant gonadotropins to establish a safer and more consistent method of human gonadotropin collection that met the high demand for its use in fertility treatments.

Josef Warkany studied the environmental causes of birth defects in the United States in the twentieth century. Warkany was one of the first researchers to show that factors in the environment could cause birth defects, and he helped to develop guidelines for the field of teratology, the study of birth defects. Prior to Warkany’s work, scientists struggled to explain if or how environmental agents could cause birth defects. Warkany demonstrated that a deficiency or excess of vitamin A in maternal nutrition could cause birth defects. He also established that mercury in teething powders increased infant mortality rates. Warkany showed how substances outside the human body could adversely affect conception, growth, and development of the human fetus in utero.

The article Experimental Studies on Congenital Malformations was published in the Journal of Chronic Diseases in 1959. The author, James G. Wilson, studied embryos and birth defects at the University of Florida Medical School in Gainesville, Florida. In his article, Wilson reviewed experiments on birds and mammals from the previous forty years to provide general principles and guidelines in the study of birth defects and teratogens, which are things that cause birth defects. Those principles included what species are convenient for conducting teratological research, what principles act in human embryological and fetal development, and what agents impact those processes. Wilson's article was one of the first attempts in the twentieth century to synthesize basic research conducted in the field of teratology. The article helped to establish teratology as a field in medicine during the twentieth century.

Sidney Q. Cohlan studied birth defects in the US during the twentieth century. Cohlan helped to discover that if a pregnant woman ate too much vitamin A her fetus faced a higher than normal risk of teratogenic effects, such as cleft palate. A teratogen is a substance that causes malformation of a developing organism. Cohlan also identified the teratogenic effects of several other substances including a lack of normal magnesium and prenatal exposure to the antibiotic tetracycline. Cohlan's experiments with vitamins and other chemicals brought attention to how nutrition and environmental agents adversely affect human pregnancy outcomes.

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.

In 2007, Ishola Agbaje, Deirdre Rogers, Carmel McVicar, Neil McClure, Albert Atkinson, Con Mallidis, and Sheena Lewis published “Insulin Dependent Diabetes Mellitus: Implications for Male Reproductive Function,” hereby “Diabetes Mellitus: Implications,” in the journal Human Reproduction. In their article, the authors explore the effects of elevated blood sugar in the form of diabetes mellitus on the quality of male sperm. When investigating possible fertility issues, fertility specialists often study semen, the male reproductive fluid that contains sperm cells to detect changes in sperm count, movement, and structure. In “Diabetes Mellitus: Implications,” the authors use both conventional semen analysis and technical molecular methods to assess the quality of sperm from diabetic and non-diabetic men. The authors found that men with diabetes had higher levels of DNA damage within their sperm and highlighted a need for additional research on the link between diabetes and male reproductive health.

This project focuses on the history of how teratogens, or agents which have the potential to cause birth defects, have been understood and tested for teratogenic potential in the US over the twentieth century. Prior to this time, teratogen studies were primarily concerned with cataloguing defects rather than exploring possible causes. At the turn of the twentieth century, experimental teratogen studies with the aim of elucidating mechanisms commenced. However, these early studies did not aim to discover human pregnancy outcomes and ways to prevent them, but simply focused on the results of exposing pregnant mammals to various physical and chemical insults.

Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Alcohol and cocaine are examples of such substances. Exposure to the teratogen affects the fetus or embryo in a variety of ways, such as the duration of exposure, the amount of teratogenic substance, and the stage of development the embryo or fetus is in during the exposure. Teratogens may affect the embryo or fetus in a number of ways, causing physical malformations, problems in the behavioral or emotional development of the child, and decreased intellectual quotient IQ in the child. Additionally, teratogens may also affect pregnancies and cause complications such as preterm labors, spontaneous abortions, or miscarriages. Teratogens are classified into four types: physical agents, metabolic conditions, infection, and finally, drugs and chemicals.